EFFECTS OF AEROSOLIZED PENTAMIDINE ON GLUCOSE-HOMEOSTASIS AND INSULIN-SECRETION IN HIV-POSITIVE PATIENTS - A CONTROLLED-STUDY

Objective: Intravenous pentamidine induces hypo- and hyperglycaemia (d ose-dependent toxicity on islet beta cells), pancreatitis and nephroto xicity. Conversely, aerosolized pentamidine (AP) is usually devoid of systemic side-effects: few reports of hypo- or hyperglycaemia have bee n published. Our study aimed to assess the influence on glucose homeos tasis and insulin secretion of long-term exposure to AP used for proph ylaxis of Pneumocystis carinii pneumonia in HIV-positive patients, and to compare the impact on insulin secretion of AP, whether administere d for the first time or after prolonged monthly exposure. Design: Retr ospective cross-sectional controlled study (main objective) and nonran domized prospective controlled study. Patients: We compared glucose ho meostasis and C peptide response to 1 mg intravenous glucagon in patie nts who had previously inhaled greater than or equal to 10 prophylacti c aerosols (group 1, n = 21) and in HIV-positive controls (groups 2 an d 3, n = 28) who had received none. Both groups were comparable for ag e and body-mass index, but CD4 T-lymphocyte counts and Karnofsky score s were both significantly higher in the control group. Results: Fastin g (T-0) blood glucose, fructosamine and response to the first glucagon test were similar in both groups, but postprandial glucose, glycated haemoglobin and fasting C peptide were significantly higher (P<0.05) i n the pentamidine group. A second glucagon test was performed on the s ame day, 3h (T-3) after AP inhalation in 35 patients (in 21 after grea ter than or equal to 10 aerosols, group 1; in 14 after the first, grou p 2) and in 14 HIV-positive controls (group 3). The only significant d ifference between the three groups in C peptide response to this secon d test was a lower peak T-3/peak T0 ratio in group 1. Plasma amylase a nd creatinine were not altered by the aerosol. Conclusion: Long-term p rophylactic exposure to AP had minor but significant effects on glucos e homeostasis and insulin secretion but did not modify pancreatic and renal function. The detrimental effects induced by long-term exposure to AP found in our study are probably not clinically relevant, but a m ore prolonged exposure to AP might conceivably induce more severe alte rations.